This is a neoplastic proliferation of a single plasma cell clone that results in excessive production of a specific immunoglobulin referred to as the M protein, myeloma protein, monoclonal protein, or paraprotein. At present, no identifiable cause for this disorder is known. The frequency of multiple myeloma increases with age in persons 40 years of age or older with a peak incidence in the seventh decade. Multiple myeloma accounts for 1% of all types of malignancy and approximately 10% of all hematologic malignancies. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma may precede the diagnosis or patients may not be diagnosed until symptomatic.
Patients with this disorder present with various symptoms or lab abnormalities including hypercalcemia, bone pain, renal impairment, plasmacytomas, hyperviscosity syndrome (retinal hemorrhage, prolonged bleeding, and neurologic changes), lytic lesions on radiographs, cord compression, or a normocytic anemia. These patients are very susceptible to bacterial infections particularly pneumococcal pneumonia. Amyloidosis may occur in 10% of patients afflicted with this disorder and may manifest as congestive heart failure, cardiac conduction defects, macroglossia, joint swelling, and peripheral neuropathy. Characteristic lab abnormalities include an extremely low anion gap, an elevated creatinine, an elevated serum total protein, hypercalcemia, isotonic hyponatremia, an elevated ESR with a normal C reactive protein (CRP), and a normocytic anemia. Also, proteinuria may be negative when evaluated by the dipstick method but frank proteinuria will be detected when the sulfosalicylic acid test is employed. This is characteristic of Bence Jones proteinuria. Patients with monoclonal proteinemia without end organ damage have either smoldering myeloma (either a monoclonal protein >3 g/dL or >10% plasma cells on bone marrow exam or both) or monoclonal gammopathy of undetermined significance (both a monoclonal protein level < 3g/dL and <10% plasma cells on bone marrow study).
The diagnosis may be established via several means. Serum protein electrophoresis (SPEP) shows a spike (M protein) in the gamma region in 75% of cases, hypogammaglobulinemia in 15%, and no abnormality in 10%. The monoclonal protein detected most often is IgG (60%), IgA (20%), Bence Jones proteinemia (10%), and IgD (1%). Seventy-five percent of patients show a globulin peak on urine protein electrophoresis (UPEP). SPEP and UPEP may be followed by immunofixation to determine the immunoglobulin class. When there is an M protein patients have heavy chain disease. When SPEP and UPEP are negative but the diagnosis is still strongly suspected (non-secretory disease or light chain myeloma) based on case findings, then measurement of serum free light chain assay may prove helpful. Elevations of kappa (0.33-1.94 mg.dL) or lamda (0.57-2.63 mg/dL) light chains will be reflected in abnormalities in the kappa/lambda ratio and are indicative of light chain disease. The normal ratio is between 0.26 to 1.65. Low ratios indicate overproduction of lambda chains and an elevated ratio is consistent with kappa chain overproduction. Either abnormality should prompt further work-up with bone marrow examination. Bone marrow biopsy yields a marrow with greater than 10% plasma cells in patients with multiple myeloma.
Prognosis can be estimated based on the results of plasma cell fluorescence in situ hybridization (FISH), metaphase cytogenetics, and plasma cell labeling index (PCLI). On FISH testing, patients with hyperploidy and translocation 14;16 have better outcomes. A PCLI greater than three portends high-risk disease. The International Staging System uses the serum albumin and beta-2 microglobulin levels. Patients are stage I when the albumin is greater than 3.5 g/dL and the beta-2 microglobulin level is less than 3.5 microg/mL. Stage III is defined by a beta-2 microglobulin level greater than 5.5 microg/mL. Stage II entails all others.
Radiographic abnormalities include punched-out lytic lesions, osteoporosis, or fractures. Frequent sites of bony involvement include vertebrae, skull, thoracic cage (ribs, sternum, and vertebra), pelvis, and the proximal portion of both the humerus and femurs. Cord compression may occur and the diagnosis should be aggressively sought in patients who present with acute lower extremity weakness and urinary or fecal incontinence. The bone disease of multiple myeloma presents with hypercalcemia with a normal alkaline phosphatase level. This is because the bone disease of multiple myeloma is secondary to osteoclastic activity without osteoblastic activity. Death commonly results from bacterial infections or renal failure. The most important factor in myeloma renal failure is the presence of Bence Jones proteinuria. While some suffer a rapidly progressive and treatment resistant disease, others have a relatively slow course to their disease.
There are multiple forms of therapy. Older regimens included vincristine, doxorubicin, and dexamethasone to rapidly induce remission. Currently, thalidomide, lenalidomide, and bortezomig are being used with consideration of stem cell transplantation. Consultation with a hematologist/oncologist is essential in the treatment of the myeloma patient. Patients should receive pneumococcal and influenza vaccinations with aggressive surveillance and treatment of bacterial infections (avoid potentially nephrotoxic antibiotics). The bisphosphonates (pamidronate 60-90 mg intravenously over 2 to 4 hours or zolendronic acid 4 mg intravenously over 15 minutes) are helpful in the treatment of hypercalcemia, and may decrease the incidence of pathologic fractures, spinal cord compression, the need for irradiation, and bone pain, thus improving quality of life. The anemia associated with myeloma may respond to erythropoietin therapy. Cord compression and cauda equina syndrome require steroids and radiation therapy, with surgical intervention when necessary. Adequate daily hydration and avoidance of NSAIDs help preserve renal function. Plasmapheresis is employed to treat symptoms of the hyperviscosity syndrome.